Currently natural human pituitary hormones such as thyrotropin (TSH) are available in only limited supply and these preparations may be contaminated with pathologic viruses. Thus is has not been possible to prepare detailed biochemical, physicochemical, biologic or therapeutic studies with such preparations. Moreover, the factors controlling pituitary hormone gene expression are poorly understood. We have recently cloned and sequenced the complete human TSH-beta subunit gene and have partially defined its thyroid hormone regulatory region. Using cotransfection experiments with a human alpha subunit cDNA and human TSH- beta genomic DNA, we have also produced synthetic human pituitary TSH. Although apparently containing more sialic acid than natural TSH, this synthetic TSH is equally active in vitro and will be used to define additional biochemical aspects and therapeutic actions of the hormone. We also plan to define other regulatory regions of the gene to gain insight into the fundamental mechanisms of transcriptional control.